This section provides background information related to the present disclosure which is not necessarily prior art.
There is an ever growing need for apparatuses and methods for taking accurate photometric measurements of liquids at increased throughputs. The pharmaceutical industry, for example, may be required by government agencies to perform tests on hundreds of thousands of drugs specimens prior to receiving approval to market certain drugs. The potential marketability of specific drugs must overcome the substantial barrier of possessing a marketability potential great enough to justify the financial cost of such laborious and time consuming testing. The cost of such testing is not solely born by pharmaceutical companies as at least some of the cost is passed on to consumers. Additionally, there is a great social cost resulting, at least partially, from the high cost of bringing pharmaceuticals to market. Because a high level of market potential is required to justify the research and development of pharmaceuticals, including the cost of testing of said pharmaceuticals as required by government agencies, there is a tendency within the pharmaceutical industry toward researching and developing products which address ailments of the affluent while neglecting to address ailments which disproportionality affect poor populations.
One variable which has a considerable effect on the accuracy of a reading is the ability to control the optical path length of a volume of a specimen fluid. The optical patent length simply refers to the distance that light travels through a specimen fluid prior to being measured once it exits the fluid. Spectrometers, for example, are commonly used to measure the optical properties of light after it has exited a test specimen but the optical properties of the exiting light is a function of the distance through which it travels through a medium, e.g. the specimen fluid. Therefore, controlling the optical path length is of great importance in obtaining accurate photometric measurements of a fluid and, resultantly, certain apparatuses address this issue.
A variety of cuvette designs exist to control the optical path length of a specimen fluid by comprising geometrical constraints over a volume of specimen fluid within the bottom of an inner region of the cuvette. As a result, the controlled optical path length is created when light is projected through one side of the cuvette and is measured on the opposite side of the cuvette. For example, U.S. Pat. Appl. Pub. No. 2012/0156796 A1, with applicants Drechsler et al., a Pub. Date of Jun. 21, 2012, and which is fully incorporated by reference herein, discloses a cuvette for photometric measurement of liquids, wherein the cuvette comprises a lower measurement chamber. The optical path length may be measured horizontally across a portion of the lower measurement chamber and, more specifically, the optical path length may be the distance between a lower front wall and a lower back wall. Some cuvettes exist which comprise two different optical path lengths based on the from which side of the cuvette the beam of light is projected. For example, the Eppendorf UVette® allows for a user to choose between two optical path lengths, e.g. 10 mm and 2 mm, with a single 90° rotation. Cuvette designs such as these examples are also particularly useful when testing requires a very small optical path length, for example a very dark fluid may require a small optical path length because a measurable amount of light might not exit the fluid if the length is too long.
A standard tool analytical research and clinical diagnostic testing laboratories, wherein large numbers of tests must often be run, is a flat plate with a plurality of wells known as a microtitre plate or simply a microplate. It is typical for a microplate to have upward of 1536 sample wells, although larger microplates have been manufactured. Each of the plurality of wells essentially serves as small test tube or cuvette and are commonly filled with volumes of specimen fluid to have photometric measurements taken. The measurements often must be taken by projecting light in the vertical direction, e.g. from above the microplate wells, to have a reading photometric measurement taken from below the microplate. The optical path length is thus dependent on the fill level of each well and so care must be taken to control the optical path length by controlling the volume added to each well. As the size of the wells in decreased in order to produce more wells per microplate this problem becomes exacerbated by the effects of surface tension. Surface tension along the perimeter of a sample well may form a meniscus at the top surface of the specimen fluid which may decrease the accuracy of a photometric measurement.
The various attempts at improving the available apparatuses and methods of taking accurate photometric measurements of liquids suffer any or all of: requiring individual treatment of each specimen, e.g. various cuvettes with lower measurement chambers designed for a horizontal optical path length must be placed one at a time into a spectrometer for photometric measurement; and requiring very tight control over the volume of specimen fluid placed within the measurement chamber, e.g. the effective optical path through which a light is projected through a specimen fluid is highly dependent on the volume of specimen fluid introduced into the well.
Therefore, there is a need for apparatuses and methods which allow for large numbers of tests to be conducted quickly and efficiently without the need for tight control over specimen fluid volumes. Such apparatuses and methods will likely have the positive effects of reducing the overall cost of healthcare. Moreover, such apparatuses and methods may increase the amount of research and development that companies can dedicate to ailments of the world's more needy and less affluent populations by reducing the cost of testing and, resultantly, increasing the number of potential drugs which companies can justify financial investment in.
Accordingly, this application discloses apparatuses and methods which allow for a high degree of control over the optical path length of a specimen fluid whilst taking photometric measurements in the generally vertical orientation such as is desirable for performing many tests in a short time period, for example on a microplate comprising a plurality of sample wells.